Real-world clinical outcomes following treatment intensification with GLP-1 RA, OADs or insulin in patients with type 2 diabetes on two oral agents (PATHWAY 2-OADs)

Introduction Most patients with type 2 diabetes require sequential addition of glucose-lowering agents to maintain long-term glycemic control. In this retrospective, observational study, we compared intensification with a glucagon-like peptide-1 receptor agonist (GLP-1 RA), oral antidiabetic drugs (OADs), and insulin in patients receiving two OADs, using US electronic health records and claims data. Research design and methods For inclusion, patients in the IBM MarketScan Explorys database were required to have claims for two different OADs in the 180-day baseline period and ≥1 claim for a different OAD/GLP-1 RA/insulin at index date (treatment intensification). Changes in glycated hemoglobin (HbA1c) and weight from baseline were assessed at 180 days postindex. Patients were propensity score-matched by baseline characteristics and exact-matched by HbA1c category (HbA1c cohort and weight/composite outcomes cohort) and body mass index (BMI) category (weight/composite outcomes cohort only) to obtain balanced treatment arms. The primary endpoint was the percentage of patients reaching target HbA1c <7% (53 mmol/mol). Results Significantly more patients intensifying with a GLP-1 RA achieved HbA1c <7% than those receiving OAD(s) (OR: 1.35; 95% CI 1.03 to 1.77; p=0.032) or insulin (OR: 1.77; 95% CI 1.27 to 2.47; p<0.001). GLP-1 RAs were also associated with a significantly greater chance of not gaining weight; significantly greater HbA1c and weight decreases from baseline; and a significantly greater chance of HbA1c <7%, no weight gain and discontinuation of ≥1 baseline OAD (composite outcome), compared with OAD(s) or insulin. Conclusions In propensity score-matched cohorts, GLP-1 RAs demonstrated significant benefits for both glycemic control and weight management over additional OAD(s) or insulin, respectively, indicating that they may represent the optimal choice at these points in the treatment pathway.